Miércoles 14 de Junio de 2006, Ip nº 157

Does My Diet Fit My Genes?
Por Christine Gorman

You are what you eat, or so the saying goes. But a new generation of molecular biologists is starting to give that old adage a decidedly high-tech twist. By combining the latest discoveries in human genetics with a deeper understanding of the hundreds of compounds found in food, investigators have begun to tease apart some of the more complex interactions between your diet and your DNA. In the process, they hope eventually to give consumers more personalized advice about what to eat and drink to stave off heart disease, cancer and other chronic conditions of aging. "We are trying to put more science behind the nutrition," says Jose Ordovas, a geneticist at the Friedman School of Nutrition at Tufts. "We want to finally understand why nutrients do what they do and to whom--why a low-fat diet may not work for some but works for others."

Do you drink three cups or more of coffee a day? Genetic tests can now determine whether you--like approximately 10% to 20% of the population--have a specific genetic variation that makes it harder for your body to absorb calcium in the presence of caffeine, thus increasing your rate of bone loss.

Are you getting enough folic acid, found in beans, peas and fortified grains? Researchers have learned that many people have a genetic predisposition that puts them at greater risk of developing heart disease because they need more folic acid than the average person to maintain normal blood chemistry.

Would a high-fat diet be particularly damaging to your health, given your genetic makeup? About 15% of folks are born with a form of a liver enzyme that causes their HDL, or good cholesterol, level to go down in response to dietary fat. In most people the HDL level goes up, counterbalancing some of the bad effects of dietary fat on LDL--the dangerous cholesterol.

This area of research is so new, there's still a bit of a debate over what exactly to call it. Nutritional genetics? Nutritional genomics? Nutrigenomics? But by any name, the field is growing fast. Indeed, some start-up companies simply aren't waiting for all the scientific mysteries and subtleties to be worked out and have begun to offer tests for a limited number of gene-nutrient interactions directly to consumers.

None of those genetic variations are immediately life threatening. In fact, most of them have no apparent effect. The variants are not like the mutations most of us learned about in school--alterations that cause entire genes or series of genes to malfunction and that result in diseases like sickle-cell anemia and cystic fibrosis. Instead the changes nutritional geneticists are looking for are more like normal variations in the correct spelling of a word--say, theatre or theater, depending on whether you speak the Queen's English or American. "We all have these variants in our genes," says Ray Rodriguez, a geneticist at the University of California at Davis. "And they affect how we absorb, utilize and store various nutrients."

In the case of genes, of course, the alphabet contains just four letters, or bases: A, T, C and G (for adenine, thymine, cytosine and guanine). "A gene has millions of bases," says Dr. Andrew Greenberg, director of the Obesity and Metabolism Laboratory at Tufts University. "We're trying to find what's called a single-nucleotide polymorphism, which is a single change in the DNA, a single base." Sometimes a single-nucleotide polymorphism (or SNP, pronounced snip) leads to the production of a slightly different version of a protein or enzyme. Sometimes that kind of change causes a shift in an individual's biochemistry or metabolism, but most of the time it doesn't.

Greenberg's research is focused on a protein called perilipin, which coats the surface of stored fat in fat cells. "I know perilipin helps regulate the breakdown of fat," he explains. But Greenberg is trying to find out whether there are normal variations in the gene that codes for perilipin that affect a person's risk of becoming obese or developing diabetes. In a study conducted with Ordovas of 1,600 people in Valencia, Spain, Greenberg determined that some of the mutations do seem to correspond to a thinner physique and reduced glucose and triglyceride levels. But other variations in the same gene seem to predispose women to be heavier and have less healthy results in blood tests.

That's the tricky thing about this new, more individualized exploration of genetics. The effect of a polymorphism may vary depending on where in a gene it is found and the influence of other genes. And a particular alteration can have varying effects in different populations. For instance, a variant gene called apolipoprotein E4 seems to increase the risk of developing Alzheimer's disease if you are Caucasian or Japanese but not if you are a black African. It's important to know not only the SNPs but also their context to understand "who will respond and who will not respond," says Ordovas.

And what if you can't wait until the science is settled? Well, you could always turn to one of the start-up biotech firms that are providing limited genetic testing for about $250. "We have 19 genes we've identified that have a clear and defined response to diet and environmental or lifestyle choices," says Rosalynn Gill-Garrison, a molecular biologist who helped found the Sciona company in 2000. Worried about that caffeine-calcium link? Sciona tests for that, as well as genetic variants that affect insulin sensitivity, cholesterol levels and more.

The test, which is sold online and at some drugstores, is simple. You use a special stick to swab the inside of your cheek, then send the sample off, along with a questionnaire about your diet and lifestyle, to Sciona's laboratories in New Haven, Conn. Within three weeks, Sciona sends back a standard computerized analysis of your survey answers, with a few highlights from or red flags about the genetic-test results. For example, Gill-Garrison says, the company estimates from the questionnaire the amount of folic acid in your system. Then it tells you what level you should be aiming for, based on the results of your genetic test.

Sciona's customers are going to have to wait a while for more comprehensive genetic exams. Researchers now have a good reference guide for the 25,000 or so genes of the human genome and the more than 3 million common variants that lurk within those genes. They still need to figure out how all those genetic variables relate to health and disease. Add the fact that food is full of hundreds of bioactive compounds, each of which varies depending on where plants are grown or animals are raised, and you've got quite a lot of information to puzzle out. In the end, you'll probably find out you still need to eat your broccoli. But at least you'll have a better understanding of why.

  11/06/2006. Time Magazine.